Comparative genomics of ESBL-producing Escherichia coli (ESBL-Ec) reveals a similar distribution of the 10 most prevalent ESBL-Ec clones and ESBL genes among human community faecal and extra-intestinal infection isolates in the Netherlands (2014-17)

Abstract

Introduction: The human gut microbiota is an important reservoir of ESBL-producing Escherichia coli (ESBL-Ec). Community surveillance studies of ESBL-Ec to monitor circulating clones and ESBL genes are logistically challenging and costly.

Objectives: To evaluate if isolates obtained in routine clinical practice can be used as an alternative to monitor the distribution of clones and ESBL genes circulating in the community.

Methods: WGS was performed on 451 Dutch ESBL-Ec isolates (2014-17), including 162 community faeces and 289 urine and blood isolates. We compared proportions of 10 most frequently identified STs, PopPUNK-based sequence clusters (SCs) and ESBL gene subtypes and the degree of similarity using Czekanowski's proportional similarity index (PSI).

Results: Nine out of 10 most prevalent STs and SCs and 8/10 most prevalent ESBL genes in clinical ESBL-Ec were also the most common types in community faeces. The proportions of ST131 (39% versus 23%) and SC131 (40% versus 25%) were higher in clinical isolates than in community faeces (P < 0.01). Within ST131, H30Rx (C2) subclade was more prevalent among clinical isolates (55% versus 26%, P < 0.01). The proportion of ESBL gene blaCTX-M-1 was lower in clinical isolates (5% versus 18%, P < 0.01). Czekanowski's PSI confirmed that the differences in ESBL-Ec from community faeces and clinical isolates were limited.

Conclusions: Distributions of the 10 most prevalent clones and ESBL genes from ESBL-Ec community gut colonization and extra-intestinal infection overlapped in majority, indicating that isolates from routine clinical practice could be used to monitor ESBL-Ec clones and ESBL genes in the community.

Figure 1.

Neighbour-joining trees. (a) Core genome – nodes coloured according to ST (10 most frequent), (b) accessory genome – nodes coloured according to ST (10 most frequent) and (c) core genome ST131 – nodes coloured according to clade (nodes with a singleton fimH type indicated separately). Constructed with PopPUNK. Online view core tree (https://microreact.org/project/Vmycsy2gY/938965ce), accessory tree (https://microreact.org/project/f9Iums0yo/11f42f48), core genome ST131-subtree (https://microreact.org/project/Vmycsy2gY/107f9879). Sample: community urine (CA), nosocomial urine (HA).

Figure 2.

Proportions of the 10 most frequent genetic subtypes in clinical isolates for (a) STs, (b) SCs and (c) ESBL gene types. Proportions of ST131, SC131 and bla_CTX-M-1 differed between clinical and community faecal isolates; P < 0.01. P value derived from χ² statistic. All other proportions did not differ significantly. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

Figure 3.

Mean observed PSI (PSI_obs), interpreted as the proportion of overlap between community faeces with clinical isolates; PSI_obs (green) with 95% CI calculated with 5000 bootstrap iterations. Permutation distribution with mean expected PSI (PSI_exp) under the null hypothesis (i.e. no difference between groups); PSI_exp (grey), calculated with 5000 permutations. P value permutation test; chance of the observed PSI under the null hypothesis (i.e. no difference between community faeces and clinical isolates). This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

Figure 4.

Mean (95% CI) PSI, interpreted as the aggregate proportion of overlap between community faeces and clinical subgroups on ST-, SC- and ESBL gene-level. Each cell is coloured according to the PSI level, with a colour gradient from 0 (light) to 1 (dark). This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.